For many therapeutic compounds to achieve effective bioavailability and solubility, they must dissolve in gastric fluid and permeate intestinal membranes. The efficacy of therapeutic compounds is generally hindered if they are metabolized too rapidly before, during, or immediately after absorption. For example, the generally low bioavailability of curcumin is attributed to its extremely low aqueous solubility and high rate of metabolism. However, once solublized, curcumin is capable of being effectively absorbed through intestinal membranes and has great potential to prevent and treat a wide spectrum of diseases such as cancer, Alzheimer's disease, inflammatory bowel syndrome, arthritis, etc. Regular consumption of curcumin or curcuminoids has been shown to delay or prevent these diseases. For example, current research has shown that the anti-cancer properties of curcumin may be due to its inhibition of NFKB activation, JNK and AP-1 transcriptional activity. It is well documented that curcumin acts as a potent inhibitor of NFKB signaling pathway which is involved in apoptosis as well as its function has been implicated in inflammation, cell proliferation, differentiation and cell survival. Although curcumin possesses anti-cancer and anti-inflammatory properties, among others, it is still considered extremely safe when administered at very high doses. Conversely, systemic toxicity at high dose rendered other anti-cancer drugs unsuitable for cancer therapy. It was recently reported that uptake of curcumin is safe at doses ranging from 3600-8000 mg/day for four months. In one clinical trial, no toxic effects were seen in patients taking curcumin at a dose of 8 g/day for 18 months.
Despite its therapeutic benefits and non-toxicity at high doses, curcumin has restrictive clinical application because of its extremely low aqueous solubility, rapid systemic metabolism and degradation at alkaline pH, which severely curtails its bioavailability. With respect to solubility, curcumin shows extremely low solubility in aqueous solutions (less than 1 μg/ml in water without any solubility enhancement techniques), but it is soluble in organic solvents such as DMSO, ethanol, methanol, and acetones. Its degradation kinetics have also been reported under various pH conditions, showing relative stability at acidic pHs (i.e., stomach) but unstable at neutral and basic pHs. It has also been reported that most curcumin (>90%) is rapidly degraded within 30 min at pH 7.2 and above. Studies have suggested that this low aqueous solubility, high degradation of curcumin at physiological pHs, and faster metabolism consequently leads to poor absorption, low tissue distribution, and rapid excretion of curcumin that severely restrict its bioavailability. Therefore, a patient must consume large doses of curcumin and curcuminoids in order to achieve detectable serum concentrations needed for its therapeutic benefits. Additionally, the low bioavailability and solubility of curcumin hinders the incorporation of curcumin and curcuminoids into effective pharmaceutical and nutraceutical formulations for both animals and humans.
To address the issues of low aqueous solubility and bioavailability of curcumin, several approaches have been explored, including the use of adjuvants to delay its metabolism and the use of excipients to enhance its bioavailability. However, the adjuvants and excipients thus far identified are not compatible with the use of curcumin and curcuminoids as a regular supplement due to their high costs and lack of practicability. Although adjuvants have been shown to delay or inhibit the metabolism of curcumin and curcuminoids, inhibiting or delaying their metabolism alone without enhancing their solubility will not result in an effective formulation. Therefore, there is a need for a formulation that enhances the bioavailability and solubility of curcumin, such that the therapeutic benefits of this compound can be fully realized.